经腹主动脉灌注瑞芬太尼聚己内酯对脊髓缺血再灌注损伤中脊髓能量代谢的影响

目的:观察腹主动脉内灌注Mu阿片受体激动剂REM-PCL对兔脊髓缺血再灌注损伤(SCIRI)中脊髓能量代谢的影响。方法:30只健康新西兰大白兔随机分为对照组(C组)、REM-PCL组(RP组,0.1 mg·kg^-1)和REM-PCL+ GSK1521498组(RG组,0.1 mg·kg^-1 REM-PCL+1 mg·kg^-1 GSK1521498),每组10只。采用肾下腹主动脉阻断法,建立SCIRI模型。分别于缺血前、缺血45 min及再灌注60 min时,取脊髓测定腺苷酸(ADP、AMP、ATP、TAN、EC)、Mu阿片受体表达、活性氧(ROS)、丙二醛(MDA)含量、线粒体肿胀度(MSD)、总抗氧化能力(T-AOC) 并观察其病理学改变。分别于缺血前、缺血45 min、再灌注30 min及再灌注60 min监测血清神经特异性烯醇化酶(NSE)浓度变化。结果:与缺血前比较,缺血45 min及再灌注60 min时C组和RG组ATP、EC、TAN、T-AOC及Mu阿片受体表达均降低(P<0.01),ROS、MDA和MSD均升高(P<0.01);RP组在缺血45 min时和再灌注60 min时ATP、T-AOC、TAN、EC及Mu阿片受体表达均显著高于C组和RG组(P<0.01),ROS、MDA和MSD含量均显著低于C组和RG组(P<0.01),RP组脊髓灰质的病理损害程度明显轻于C和RG组(P<0.01)。缺血45 min、再灌注30 min及再灌注60minRP组血清NSE浓度明显低于C组和RG组(P<0.01)。结论:腹主动脉内灌注REM-PCL通过激活Mu阿片受体能够明显改善SCIRI中脊髓能量代谢,保护脊髓线粒体的结构,从而减轻SCIRI。

Effects of REM-PCL infusion through abdominal aorta on energy metabolism of spinal cord during spinal cord ischemia-reperfusion injury

OBJECTIVE To observe influences of infusing Mu-opioid receptor (MOR) agonist REM-PCL through abdominal aorta on spinal cord energy metabolism during spinal cord ischemia-reperfusion injury (SCIRI). METHODS SCIRI model was created by clamping infrarenal aorta in thirty healthy New Zealand white rabbits, which were randomly divided into control group (physiological saline, group C, n=10), REM-PCL group (0.1 mg·kg^-1, group RP, n=10) and REM-PCL+GSK1521498 group (0.1 mg·kg^-1 REM-PCL+1 mg·kg^-1 GSK1521498, group RG, n=10). Spinal cord tissues were obtained before ischemia, 45 min after ischemia and 60 min after reperfusion for determination of spinal cord contents of adenine nucleotide (ADP, AMP, ATP, TAN and EC), levels of MOR, reactive oxygen species (ROS), malondialdehyde (MDA), mitochondrial swelling degree (MSD), total anti-oxidation capacity (T-AOC) and pathological changes by HE staining. Concentration of serum neuron-specific enolase (NSE) was monitored before ischemia, 45 min after ischemia, 30 min and 60 min after reperfusion. RESULTS Spinal cord contents of ATP, EC, TAN, MOR and T-AOC were decreased while ROS, MDA and MSD were increased at 45 min after ischemia and 60 min after reperfusion as compared to values before ischemia in C and RG groups (P<0.01). ROS, MDA and MSD were distinctly lower while ATP, EC, TAN, MOR and T-AOC were distinctly higher at 45 min after ischemia and 60 min after reperfusion in group RP than in C and RG groups (P<0.01). Change of pathological damage to gray matter of spinal cord was more serious in C and RG groups at 45 min after ischemia and 60 min after reperfusion than those in group RP (P<0.01). Serum level of NSE was significantly higher in C and RG groups at 45 min after ischemia, 30 min and 60 min after reperfusion than that in group RP (P<0.01). CONCLUSION Intra-aortic REM-PCL infusion by Mu opioid receptor activation can distinctly ameliorate energy metabolism of spinal cord and protect spinal cord mitochondria to attenuate SCIRI.